NASA-funded scientists are crafting microscopic vessels
that can venture into the human body and repair problems 
one cell at a time.

January
15, 2002: It's like a scene from the movie "Fantastic
Voyage." A tiny vessel -- far smaller than a human cell
-- tumbles through a patient's bloodstream, hunting down diseased
cells and penetrating their membranes to deliver precise doses
of medicines.

Only this isn't Hollywood. This is real science.

Right: Tiny capsules much smaller than these blood
cells may someday be injected into people's bloodstreams to treat
conditions ranging from cancer to radiation damage. Copyright
1999, Daniel Higgins, University of Illinois at Chicago.

Researchers funded by a grant from NASA recently began a project
to make this futuristic scenario a reality. If successful, the
"vessels" developed by these scientists -- called nanoparticles
or nanocapsules -- could help make another science fiction story
come true: human exploration of Mars and other long-term habitation
of space.

While space applications will be the researchers' primary
focus, nanoparticles also hold great potential for many fields
of medicine, particularly cancer treatment. The tantalizing promise
of delivering tumor-killing poisons directly to cancerous cells,
thus averting the ravaging side-effects of chemotherapy, has
generated a lot of interest in nanoparticles among the medical
community.

"The purpose of these nanoparticles is to introduce a
new type of therapy -- to actually go inside individual cells
... and repair them, or, if there's a lot of damage, to get rid
of those cells," explains James Leary of the University
of Texas Medical Branch. Leary is leading the research along
with Stephen Lloyd, and Massoud
Motamedi, also from the University of Texas; Nicholas Kotov of
Oklahoma State University; and Yuri Lvov of Louisiana Tech University.

Their project will focus on a problem related to cancer --
the high radiation doses experienced by astronauts in space,
especially on journeys to the Moon or to Mars, which require
leaving the protective umbrella of the giant magnetic field surrounding
the Earth.

Even the advanced materials used for radiation shielding on
spacecraft can't fully insulate astronauts from the high-energy
radiation of space. These photons and particles pierce the astronauts'
bodies like infinitesimal bullets, blasting apart molecules in
their path. When DNA is damaged by this radiation, cells can
behave erratically, sometimes leading to cancers.

"This is an important problem,"
Leary says. "If humans are going to live in space, we have
to figure out how to protect them from radiation better."

Because shielding alone probably won't solve the problem,
scientists must find some way to make the astronauts themselves
more resistant to radiation damage.

Nanoparticles offer an elegant solution. These drug-delivery
capsules are tiny -- only a few hundred nanometers, which is
smaller than a bacterium and smaller even than the wavelengths
of visible light. (A nanometer is one-millionth of a millimeter.)

A simple injection with a hypodermic needle can release thousands
or millions of these capsules into a person's bloodstream. Once
there, nanoparticles will take advantage of the body's natural
cellular signaling system to find radiation-damaged cells.

The trillions of cells in a human body identify themselves
and communicate with each other via complex molecules embedded
in their outer membranes. These molecules act as chemical "flags"
for communicating to other cells or as chemical "gates"
that control entrance to the cell for molecules in the bloodstream
(such as hormones).

When cells become damaged by radiation, they produce markers
in a particular class of proteins called "CD-95" and
place these on their outer surfaces.

"It's
how the cell speaks to other cells and says, 'Hey, I'm injured,'"
Leary says.

By implanting molecules in the outer surface of the nanoparticles
that bind to these CD-95 markers, scientists can "program"
the nanoparticles to seek out these radiation-damaged cells.

Left: A two-layered membrane separates the cell
interior in the bottom-right of this image from the surrounding
environment. Complex molecules in this outer membrane control
how the underlying cell interacts with its surroundings. Image
copyright Scott Barrows, University of Illinois at Chicago.

If the radiation damage is very bad, nanoparticles can enter
the damaged cells and release enzymes that initiate the cell's
"auto-destruct sequence," known as apoptosis. Otherwise,
they can release DNA-repair enzymes to try to fix the cell and
return it to normal functioning.

Humans and other organisms have natural enzymes that tend
to DNA and repair mistakes, but some do a better job than others. "There
are organisms that can [absorb high] radiation doses and do just
fine," Leary says. By studying such species, scientists
have already fashioned DNA-repairing enzymes that could be delivered
by nanoparticles.

Leary's team is also studying ways to attach fluorescent molecules
to the nanoparticles. These could be designed to light up at
certain stages of the process, even employing different colors
for different stages. These fluorescent tags would provide a
way to monitor the nanoparticles within the body.

Above: In this illustration nanocapsule walls are
partially dissolved, then allowed to reform, trapping fluorescent-tagged
drug molecules inside. Such vessels can be made of self-assembling
polymers or of semiconductor materials such as cadmium telluride. Courtesy Yuri Lvov, Louisiana Tech University.

"To assess the degree of radiation damage, an astronaut
would put on something like a pair of glasses, but those glasses
peer inward onto the retina," Leary explains. "And
you use the flowing of [fluorescent] nanoparticles on cells through
the retina as sort of an in vivo assessment instrument."
(In vivo means "within the organism.")

Related technology already exists -- it's used to measure
blood flow changes in the retina due to various diseases. NASA
is interested in such non-invasive ways to monitor health because
astronauts might need to act as their own doctors on extended
missions.

"Eventually, astronauts might wear these glasses to sample
what's going on in their bloodstream. And then if they need treatment,
they have a hypodermic needle with the appropriate nanoparticles
for the job," he says.

Nanoparticles are a radically new approach to biosensing and
medicine delivery, and as such the technology will require many
more years to become mature and dependable. But it's not a pie-in-the-sky
fantasy. All the elements of this idea have already been demonstrated
separately -- the DNA-repair enzymes, the nanoparticles, the
fluorescent tags. The trick is getting them all to work together
reliably.

"This is a very difficult problem, and we're not going
to be able to do it all in three years," which is the duration
of the grant. "We're trying to do some pretty innovative
science here -- it's a bit of a jump," says Leary. "But
that's why it's a lot of fun to work on."

Biomolecular Sensor Development (NASA/Ames) -- The National
Aeronautics and Space Administration (NASA) and the National
Cancer Institute (NCI) have entered into a
collaboration to support the development of innovative minimally
invasive sensing technologies, bioinformatics, and disease intervention
strategies.